Antioxidant effects of ethyl acetate fraction of Mentha spicata (L.) were evaluated against 4-nitroquinoline-1-oxide injected mice. For this study, experiment setup consisted of 36 albino mice of either sex divided into 6 groups: Control (25% DMSO in water), ethyl acetate fraction (EAF) alone group (80, 160 mg/Kg body weight-bwt), 4-NQO (7.5 mg/Kg bwt-IP) alone and 4-NQO + EAF. EAF and vehicles were administered orally for five consecutive days. 4-NQO (7.5 mg/Kg bwt) was injected intraperitoneally on the 6th day. After 24 h, the animals were killed; liver sample was extracted and used for bio-assay. 4-NQO alone treated group decreased (27-60%) the antioxidant activities and promoted lipid peroxidation (LPO-60%) over their respective control values. Pretreatment with EAF, at the maximum dose (160 mg/Kg bwt) brought down the LPO up to 87% enhanced by 4-NQO. Among the enzymatic antioxidants, glutathione S-transferase (GST) was the most affected enzyme with 4-NQO and the least was catalase (CAT). Pretreatment with EAF (160 mg/Kg bwt), the restoration of antioxidants like glutathione peroxidase, superoxide dismutase, and CAT were found equal or less than 1.2 fold higher than that of the respective control values whereas, GST was observed to be the most restored antioxidant. Be reduced glutathione (GSH) and the least vitamin C over their control values. EAF restored the GSH and Vitamin E levels were found to be 1.2 fold higher than the respective control values.